cidpusa.org  treatment

Objective  To review the efficacy and safety of high-dose, intermittent IV methylprednisolone (IVMP) as initial and long-term maintenance therapy for patients with CIDP.

Design  A retrospective medical record review between 1992 and 2003 of outcomes in CIDP, comparing patients in 3 cohorts depending on whether their primary treatment was IVMP, IVIg, or oral immunosuppression with prednisone or cyclosporine.

Setting  Washington University Neuromuscular Disease Center (St Louis, Mo), outpatient and inpatient records.

Patients  Patients with clinical and electrophysiologic evidence of CIDP were identified. Of 57 patients, 39 had sufficient data for full analysis.

Main Outcome Measures  Quantitative muscle testing with a handheld dynamometer. Medication profiles and adverse effects were also recorded.

Results  There was no significant difference in the mean improvement in quantitative muscle testing at 6 months or at the last clinic visit (an average of 4.5 years later) among the 3 groups. Fewer patients treated with oral immunosuppression improved at 6 months, but at the last visit, 81% to 88% improved in all 3 groups. Less weight gain and fewer cushingoid features affected patients treated with IVMP (19%) compared with patients treated with oral prednisone (58%).

Conclusions  Treatment of patients with CIDP using high-dose intermittent IVMP results in improved strength equal to that with IVIg and oral prednisone. The frequency of occurrences of weight gain and cushingoid features with IVMP is less than that with oral prednisone. Intravenous methylprednisolone should be considered for initial and long-term therapy in CIDP when patients have disability due to weakness.

Corticosteroids have been used to treat CIDP for almost 50 years. Controlled trials have supported the initial impression of efficacy,^2-3 and treatment with prednisone is now accepted as a first- or second-line therapy in CIDP. Although there is no standard regimen, corticosteroid treatment of CIDP often begins with daily oral prednisone, at high doses of up to 1 mg/kg.⁴ When improved strength is noted, usually after 1 to 3 months, a slow taper in total dose is begun and an effort is made to administer the drug on alternate days. Recurrence of symptoms during the taper necessitates reinstitution of higher doses of prednisone or the introduction of an alternative agent. A major drawback to long-term oral corticosteroid use is the common occurrence of adverse effects, including weight gain, cushingoid appearance, hyperglycemia, peptic ulcer disease, insomnia, infection, cataracts, and osteoporosis.^{1, 5} Alternate-day corticosteroid treatment probably has fewer adverse effects than daily dosing.

The mechanism of action of steroids is complex and likely involves multiple effects brought about by the activation of the glucocorticoid receptor.⁶ The glucocorticoid receptor binds to glucocorticoid-responsive elements located in the promoter regions of specific genes or to other nuclear transcription factors and can activate or inhibit gene transcription. Although prednisone has an elimination half-life of 1.5 to 4 hours, some of its effects might last for days because of changes in gene expression and protein synthesis.^5-6

We began using high-dose intermittent IV methylprednisolone (IVMP) as initial and long-term maintenance therapy for many patients with CIDP in 1992 in an attempt to find an alternative treatment regimen without the problems associated with long-term daily steroids. We now report a retrospective review of all CIDP patients treated in the Washington University Neuromuscular Disease Center (St Louis, Mo) between 1992 and 2003. We compared patients treated with IVMP, IVIg, and long-term oral immunosuppression. We evaluated the efficacy of each treatment by examining changes in quantitative strength measures, medication history, and adverse effects or complications with each type of treatment.

METHODS

COMMENT

Our data show that IVMP appears to be as effective as IVIg and oral prednisone in the initial and long-term management of patients with CIDP. In patients treated with IVMP, strength, as measured by quantitative muscle testing, improved on average by 18% within the first 6 months and by 27% at the time of last follow-up, on average after 4.6 years. There were no statistically significant differences in mean improvement in strength within 6 months, or at the last follow-up, when compared with patients treated with IVIg (26% at 6 months, 31% at 3.6 years) or oral immunosuppression (12% at 6 months, 40% at 4.7 years). We also found no statistically significant difference in the frequency of improvement when comparing our 3 groups at the time of last follow-up, with more than 80% of patients improved in each group. However, within the first 6 months, more patients treated with IVMP (77%) and IVIg (100%) improved than with oral immunosuppression (38%) (P = .04). Previous studies also suggest that relatively prolonged treatment of CIDP with oral corticosteroids might be needed before patients improve.⁴ Although the presence of less severe baseline weakness in patients treated with IVMP compared with oral immunosuppression might partly explain the benefit in this group, we think it unlikely. Even though patients receiving IVMP started out with greater baseline strength, all 3 groups improved to a similar degree, suggesting similar beneficial effects from all 3 medications. Furthermore, there was no significant difference in baseline strength between patients receiving IVMP compared with IVIg, and improvement was similar in these 2 groups, suggesting that each of these 2 medications had comparable beneficial effects.

Two prior reports discuss the shorter-term use of IV corticosteroids to treat CIDP. Molenaar et al²⁵ described 10 patients treated with 6 cycles of 40 mg of dexamethasone for 4 consecutive days over 19 weeks. Three patients discontinued treatment, 1 because of adverse effects and 2 because of deterioration. The patients who completed the treatment course all had objective improvement. In another study, reported only as an abstract, 5 patients were treated with IVMP 1000 mg/d for 5 days and then with 1000 mg every 1 to 8 weeks, depending on the clinical response.²⁶ All patients had improved motor and sensory function. No adverse effects were noted except for flushing and euphoria with the infusion.

Drawbacks of our study include its open-label, retrospective nature and nonstandardized treatment regimes and evaluations. To simplify comparisons, we included patients treated with oral prednisone and oral cyclosporine in the same group. A randomized prospective trial could definitively address whether IVMP is as efficacious as IVIg or oral prednisone. However, even with these drawbacks, our data are consistent with the earlier findings that IVMP treatment is followed by improvement in strength and can be used as initial therapy in patients with CIDP, even those with severe weakness.

Our data are the first to suggest that IVMP can be used long-term for many years to maintain improved strength. One of the main drawbacks of long-term oral corticosteroid treatment is the high likelihood of adverse effects.^{1, 5} In our study, 58% of patients treated with oral corticosteroids had weight gain or cushingoid appearance. In contrast, only 19% of patients treated with IVMP had similar adverse effects. Another outcome indicated that the addition of a steroid-sparing agent was uncommon (31%) and less frequent than in patients receiving oral prednisone (100%)—suggesting a low incidence of prominent adverse effects in patients receiving IVMP. Although not statistically significant, the development of hyperglycemia or diabetes was more than 2.5 times as common in patients treated with oral prednisone compared with IVMP. Other adverse effects were rare and not significantly more common with IVMP than with oral prednisone.

The most common adverse effect in patients treated with IVMP was a 24- to 48-hour syndrome characterized by insomnia, restlessness, heartburn, flushing, sweating, and facial erythema, occurring in 38% of patients. This syndrome was transient and not severe enough to warrant discontinuation of the medication. This syndrome was as common as the transient syndrome of headache, nausea, and chills that occurred in patients treated with IVIg.

In summary, our study shows that IVMP is as effective in improving and maintaining strength as IVIg or oral immunomodulating treatments. It is much less expensive than IVIg, oral prednisone, or plasma exchange²⁷ and is easily administered over a period of a few hours in an outpatient infusion center or at home. Intermittent high-dose IVMP also has fewer adverse effects than daily administration of prednisone, whose adverse effects often limit its use. Intermittent IV methylprednisolone should be considered as an initial therapy and for long-term use in patients with weakness or disability due to CIDP.